The Bugs Inside Us All
More than half of our body is not human.
More than half of our body is not human. Rather, it’s microbes. Approximately 100 trillion of them — bacteria, fungi, viruses — inhabit all the surfaces of our bodies: the gut, the lungs, the brain, the skin. This microbial army, called the microbiome, constitutes almost a distinct organ in itself, with its very own metabolic and immune functions.
Indeed, today we know that the microbiome is in constant biological trade with the human part of our bodies, helping us digest our food, regulate our immune responses against other disease-causing bacteria, affecting behaviour and mental health. “For a long time, microbiologists assumed that the role of the microbiome in the body was passive.” says immunologist Azza Gadir. “It’s only in the past decade that we’ve come to understand the important roles the microbiome actually plays in the body.”
Gadir was introduced to the microbiome when studying how dysfunctions in the immune system can cause food allergies during her postdoc at Harvard Medical School and Boston's Children’s Hospital. “We think about it as if the immune system is like a balance,” she explains. “When you get an infectious disease, the immune system will activate to clear whatever that infectious pathogen is. But at some point, when you clear that infectious pathogen, that balance needs to come back into the middle. But if there's an imbalance at the gut, and the body is failing to tolerate something, that’s when you develop food allergies.”
In her research, Gadir specifically focused on a group of cells called regulatory T cells, that have the function to moderate immunity responses. “In people with food allergies, they don't work as well,” Gadir says. “They get confused and start to hit things that they shouldn't be hitting, like peanuts or eggs.”
What Gadir eventually discovered was that these same cells were also controlling inflammation in the microbiome. “We moved our mice from one room to the other and we saw substantial changes in their allergies, which indicated that there was something in the rooms that was causing a difference,” she says. “Spoiler alert: it was the microbiome.” Later, when she performed fecal transplantation from healthy mice to food-allergic ones, she found that those allergies were reversible. “We actually identified certain microbes that you can harness as probiotics, and use this therapy, and that could actually prevent the mice from developing food allergies.”
Gadir went on the map out how individual microbiomes evolve and, to her surprise, realised that they were determined from around the moment of birth. In one of her studies, she took faecal matter from newborn babies every six months up to the age of three to try to pinpoint the point at which food allergies could start being correctly diagnosed, finding that food allergies could already be diagnosed around the age of one. “It was very clear that that these kids had a very specific microbial signature earlier than the first year of age,“ she says “There’s always been a belief that the entire uterine environment was sterile, but now there's evidence that your microbiome develops during foetal stage and isn't something that's introduced to you after you're born.”
How babies are delivered is the single most important event in determining the composition of our microbiome. “When you're born vaginally, you are exposed to the microbes in the vaginal canal on the way out and those are the first that populate your gut,” Gadir says. “If you're born Caesarean, you're born sterile.” This, of course, has consequences later in life. Researchers have found, for instance, that mice without any bacteria reacted much stronger to stress compared to mice that had a more conventional microbiome. Other factors also contribute. Breastfeeding, for instance, transfers microbes from the mother to the newborn. Environmental exposure to bacteria and pathogens at an early age also shapes the microbiome.
According to Gadir, the profile of this individual microbiome doesn’t change much after the age of three. It can, however, be severely disrupted in its function and diversity by many factors, like stress or use of antibiotics, which indiscriminately wipe out good and bad bacteria.
A healthy microbiome, on the other hand, is characterised by its diversity. Researchers have been confirming the different ways to promote this, like eating plant-based diets, ingesting polyphenol-rich foods like soy, limiting sugar and processed foods, having a pet, living on a farm. “These are things that sound really boring, but they're actually super important to maintain a balance,” Gadir says.
At the end of her postdoctoral research, in 2018, Gadir joined microbial science company Seed as director of R&D, to further understand how microbes can help treat and prevent disease and develop microbiome-based therapeutics. “What we’re finding now is that it's not enough just to identify microbes that are associated with health or disease, it's more important to take those microbes and put them back into humans and understand how they are interacting,” she says. Using transcriptomics to identify which enzymes and proteins are being produced by the microbiomes, Seed developed products that can mimic the function of such molecules. One example is symbiotics, a combination of prebiotics and probiotics, containing more than 20 bacterial strains that perform an array of different functions in the body. “Our customers were coming back to us and saying that they were finding that their irritable bowel syndrome symptoms were going away, or that they were seeing better regulation,” she says.
Despite the progress, Gadir is aware that there’s still a lot that’s not understood about the complex interplay between our microbiomes and our health. “The science just isn't solid enough in terms of actionable things that you can do once we have data on our microbiomes,” she says “We're starting to understand their function but we still need more clinical trials to truly understand how these microbes are playing a role and interacting.”